Open AccessReceptor Activator of NF‐κB Ligand Promotes Proliferation of a Putative Mammary Stem Cell Unique to the Lactating Epithelium
Author(s) -
Thomas Elizabeth,
LeePullen Tracey,
Rigby Paul,
Hartmann Peter,
Xu Jiake,
Zeps Nikolajs
Publication year - 2012
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1092
Subject(s) - biology , rankl , microbiology and biotechnology , stem cell , placental lactogen , prolactin receptor , progenitor cell , endocrinology , mammary gland , medicine , receptor , cancer research , activator (genetics) , prolactin , hormone , placenta , cancer , breast cancer , biochemistry , fetus , pregnancy , genetics
In mice, CD49f hi mammary stem cells (MaSCs) asymmetrically divide to generate CD49f + committed progenitor cells that differentiate into CD49f − phenotypes of the milk‐secreting tissue at the onset of pregnancy. We show CD49f + primary mammary epithelial cells (PMECs) isolated from lactating tissue uniquely respond to pregnancy‐associated hormones (PAH) compared with CD49f + cells from nonlactating tissue. Differentiation of CD49f + PMEC in extracellular matrix produces CD49f − luminal cells to form differentiated alveoli. The PAH prolactin and placental lactogen specifically stimulate division of CD49f − luminal cells, while receptor activator of nuclear factor (NF)‐κB ligand (RANKL) specifically stimulates division of basal CD49f + cells. In nondifferentiating conditions, we observed a greater proportion of multipotent self‐renewing cells, and RANKL treatment activated the RANK pathway in these cultures. Furthermore, we observed the deposition of calcium nodules in a proportion of these cells. These data imply that a MaSC unique to the lactating breast exists in humans, which generates progeny with discrete lineages and distinct response to PAH. S TEM C ELLS 2012;30:1255–1264